A novel bicompartmental mathematical model of glioblastoma multiforme

Hathout, Leith; Ellingson, Benjamin M.; Cloughesy, Timothy F.; Pope, Whitney B.

doi:10.3892/ijo.2014.2741

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…Hathout et al . introduce a model that includes an advection term to account for the so-called cell streaming, where some of the tumor cells seen to stream widely along white matter pathways [ 18 ]. Other models attempt to capture the dynamics of glioblastoma multiforme by passive diffusion only [ 19 – 22 ].…”

Section: Discussionmentioning

confidence: 99%

Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme

et al. 2016

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Glioblastoma multiforme is a malignant brain tumor with poor prognosis and high morbidity due to its invasiveness. Hypoxia-driven motility and concentration-driven motility are two mechanisms of glioblastoma multiforme invasion in the brain. The use of anti-angiogenic drugs has uncovered new progression patterns of glioblastoma multiforme associated with significant differences in overall survival. Here, we apply a mathematical model of glioblastoma multiforme growth and invasion in humans and design computational trials using agents that target angiogenesis, tumor replication rates, or motility. The findings link highly-dispersive, moderately-dispersive, and hypoxia-driven tumors to the patterns observed in glioblastoma multiforme treated by anti-angiogenesis, consisting of progression by Expanding FLAIR, Expanding FLAIR + Necrosis, and Expanding Necrosis, respectively. Furthermore, replication rate-reducing strategies (e.g. Tumor Treating Fields) appear to be effective in highly-dispersive and moderately-dispersive tumors but not in hypoxia-driven tumors. The latter may respond to motility-reducing agents. In a population computational trial, with all three phenotypes, a correlation was observed between the efficacy of the rate-reducing agent and the prolongation of overall survival times. This research highlights the potential applications of computational trials and supports new hypotheses on glioblastoma multiforme phenotypes and treatment options.

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Section: Discussionmentioning

confidence: 99%

Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme

et al. 2016

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“…Glioblastoma (GBM) is an aggressive astrocytic neoplasm and one of the main contributors to cancer-associated deaths in adult and pediatric populations ( 1 ). Median survival time of GBM patients is approximately 12–15 months after the first diagnosis ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid enhances temozolomide-induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway

Shi

Yang

2017

Oncology Letters

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The present study evaluated the retinoic acid (RA) enhancement of temozolomide (TMZ) effects on the human glioma cells U251 and explored its underlying molecular mechanism. The cell growth was detected using the MTT assay and the cell cycle was assessed by flow cytometry. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and the cell morphology was evaluated using transmission electron microscopy (TEM). Additionally, reverse transcription-PCR and western blot analysis were applied to detect the mRNA and protein levels. The RA treatment in combination with TMZ in the human U251 cells further inhibited cells growth, arresting cell cycle progression at the G0/G1 phase, and significantly induced apoptosis of U251 cells. After the RA+TMZ treatment of U251 cells, autophagy associated proteins Beclin 1 and LC3B were significantly increased, and the TEM analysis were consistent with autophagy protein levels. Moreover, Keap1/Nrf2/ARE expression was downregulated significantly, indicating the involvement in the mechanisms that RA treatment could enhance the TMZ effects on U251 cells. RA treatment in combination with TMZ may provide some experimental evidence for the possible effect of RA+TMZ against the growth and the proliferation of glioma cells. Therefore, the RA+TMZ administration may have potential utility for glioblastoma treatment.

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“…Parameters (dimensional quantities) Glioma carrying capacity 10 5 − 10 8 cells/mm 3Banerjee et al 2015;Hathout et al 2014;Rockne et al 2010) …”

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confidence: 99%

Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

Kumar

Surulescu

2021

J. Math. Biol.

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Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns (not necessarily of Turing type), including pseudopalisades, can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related .

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A novel bicompartmental mathematical model of glioblastoma multiforme

Cited by 5 publications

References 34 publications

Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme

Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme

All-trans retinoic acid enhances temozolomide-induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway

Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

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